Efforts are focused on the design, synthesis and evaluation of peptides that are expected to act as inhibitors of key biochemical processes in cell proliferation and in retroviral invasion. In particular, inhibitors were designed to the HIV-1 specific proteinase, making use of the sense/anti-sense concept of molecular recognition. Recent efforts focused on evaluating the alpha-helical region-directed complementary peptides. Nineteen such 10-mer peptides were designed based on the complementary MRNA sequence, hydropathic complementarity optimization, and modulation of the basic, acidic and aromatic amino acid constituents. Five inhibitory peptides of novel structure were discovered, the most effective showing an IC50 of 30 micromoles. In other studies, various D-configuration-containing peptide segments of the cell attachment region of laminin were evaluated to probe the conformational requirements of laminin/cell surface receptor interactions. Eight linear and cyclic L- and D- configuration amino acid-containing peptides were designed to inhibit the tyrosine kinase signal transduction pathways. Two of these agents were found to inhibit PDGF-r/phosphoinositol-3-kinase interactions. The complementary peptide approach was also evaluated by designing 10 peptides targeted to the cleavage site of the proendothelin itself. Two of these agents were effective inhibitors of the proendothelin/endothelin converting enzyme. The peptide chemistry group is involved in conformational studies of relevant peptides and proteins. A distinct conformational effect of myristylation on the N-terminal 16-- mer peptide segment of the G protein, ADP ribosylation factor, was demonstrated in a circular dichroism (CD) study. Methods were developed to obtain informative data from CD spectra of proteins as films, with applicability to fibrous and membrane proteins. In applying this, as well as FT-infrared and fluorescence spectroscopy, we have demonstrated the conformational-transitions, exceptional stability, and unfolding of scrapie amyloid (prior protein).